Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. Here, combination therapy may be desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology.
For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin and with a glucagon-like peptide-1 (GLP-1), which is derived from the transcription product of the proglucagon gene. GLP-1 is found in the body and is secreted by the intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.
There are a number of potential problems when delivering two or more active medicaments or “agents” simultaneously. The two or more active agents may interact with each other during the long-term, shelf life storage of the formulation. A formulation comprising at least two active agents will preferably be understood as pre-mix/premix medicament or pre-mixed/premixed formulation in the context of this disclosure. Therefore, it is advantageous to store the active components separately and only combine them at the point of delivery, e.g. injection, needle-less injection, pumps, or inhalation. However, the process for combining the two agents needs to be simple and convenient for the user to perform reliably, repeatedly and safely.
A further problem is that the quantities and/or proportions of each active agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example one or more active agents may require a titration period to gradually introduce a patient to a “maintenance” dose. A further example would be if one active agent requires a non-adjustable fixed dose while the other is varied in response to a patient's symptoms or physical condition. This problem means that pre-mixed formulations of multiple active agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active components, which could not be varied by the healthcare professional or user.
Additional problems arise where a multi-drug compound therapy is required, because many users cannot cope with having to use more that one drug delivery system or make the necessary accurate calculation of the required dose combination. This is especially true for users with dexterity or computational difficulties.
Accordingly, there exists a strong need to provide devices and methods for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform. The present application discloses specific embodiments of methods, devices and drug delivery systems that overcome the above-mentioned concerns by providing separate storage containers for two or more active drug agents that are then only combined and/or delivered to the patient during a single delivery procedure. Setting a dose of one medicament automatically fixes or determines the dose of the second medicament (i.e., a non-user settable dose).
According to the disclosure the term medicated module is preferably used to characterize a containment or reservoir of a (secondary) drug compound within a needle sub-assembly. As such a medicated module may comprise at least one double ended needle. Furthermore a medicated module may comprise a needle guard and/or a bypass. The bypass can be any configuration, such as, a channel, pipe, conduit, groove, slot, or any other like pathway that is capable of carrying the medicament from the primary reservoir (e.g. cartridge) to the second needle or output needle without communicating with the secondary reservoir/medicament
Moreover, the opportunity may be given for varying the quantity of one or both medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g. dialing a user variable dose or changing the device's “fixed” dose). The second fluid quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of a secondary medicament. The user or healthcare professional would then select the most appropriate secondary package or series or combination of series of different packages for a particular treatment regime.
In situations where a primary medicament is used to push or flush out a secondary medicament from a separate package or reservoir, the volume of the secondary medicament in the reservoir will offset the absolute volume of the actual dose of the primary medicament that is delivered from the delivery device. Obviously, a given volume or set dose of medicament can contain a variety of concentrations of one or more drug agents depending on the formulation protocol that was used to prepare the medicament. As such, although the user sets a specific dose A of the primary medicament, in actuality only C amount of primary medicament (volume A minus the volume B of reservoir) will be delivered to the user/patient. To overcome this problem a complex technical redesign of the delivery device would be required to deliver the complete dose A and also to indicate the correct quantity or concentration of delivered primary medicament to the user in all use scenarios (e.g. if the user were to take only the primary medicament, the device would have to be able to indicate the correct dialed and received dose). In specific embodiments, our invention solves this problem by premixing the secondary medicament in the secondary reservoir with a predetermined volume of the primary medicament. In one embodiment the predetermined volume of the primary medicament may be equal to the volume of the secondary reservoir. In a further embodiment the secondary reservoir may contain the same concentration of the primary drug as does the primary reservoir.
These and other advantages will become evident from the following more detailed description of the invention.